Advanced

Monomer dimer dynamics and distribution of GPI-anchored uPAR are determined by cell surface protein assemblies

Caiolfa, Valeria R; Zamai, Moreno; Malengo, Gabriele; Andolfo, Annapaola; Madsen, Chris D LU ; Sutin, Jason; Digman, Michelle A; Gratton, Enrico; Blasi, Francesco and Sidenius, Nicolai (2007) In Journal of Cell Biology 179(5). p.82-1067
Abstract

To search for functional links between glycosylphosphatidylinositol (GPI) protein monomer-oligomer exchange and membrane dynamics and confinement, we studied urokinase plasminogen activator (uPA) receptor (uPAR), a GPI receptor involved in the regulation of cell adhesion, migration, and proliferation. Using a functionally active fluorescent protein-uPAR in live cells, we analyzed the effect that extracellular matrix proteins and uPAR ligands have on uPAR dynamics and dimerization at the cell membrane. Vitronectin directs the recruitment of dimers and slows down the diffusion of the receptors at the basal membrane. The commitment to uPA-plasminogen activator inhibitor type 1-mediated endocytosis and recycling modifies uPAR diffusion and... (More)

To search for functional links between glycosylphosphatidylinositol (GPI) protein monomer-oligomer exchange and membrane dynamics and confinement, we studied urokinase plasminogen activator (uPA) receptor (uPAR), a GPI receptor involved in the regulation of cell adhesion, migration, and proliferation. Using a functionally active fluorescent protein-uPAR in live cells, we analyzed the effect that extracellular matrix proteins and uPAR ligands have on uPAR dynamics and dimerization at the cell membrane. Vitronectin directs the recruitment of dimers and slows down the diffusion of the receptors at the basal membrane. The commitment to uPA-plasminogen activator inhibitor type 1-mediated endocytosis and recycling modifies uPAR diffusion and induces an exchange between uPAR monomers and dimers. This exchange is fully reversible. The data demonstrate that cell surface protein assemblies are important in regulating the dynamics and localization of uPAR at the cell membrane and the exchange of monomers and dimers. These results also provide a strong rationale for dynamic studies of GPI-anchored molecules in live cells at steady state and in the absence of cross-linker/clustering agents.

(Less)
Please use this url to cite or link to this publication:
author
publishing date
type
Contribution to journal
publication status
published
keywords
Cell Line, Cell Membrane, Diffusion, Dimerization, Endocytosis, Extracellular Matrix, Fluorescence Resonance Energy Transfer, Glycosylphosphatidylinositols, Humans, Models, Biological, Plasminogen Activator Inhibitor 1, Protein Binding, Protein Transport, Receptors, Cell Surface, Receptors, Urokinase Plasminogen Activator, Serum, Vitronectin, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't
in
Journal of Cell Biology
volume
179
issue
5
pages
82 - 1067
publisher
Rockefeller University Press
external identifiers
  • scopus:36849016409
ISSN
0021-9525
DOI
10.1083/jcb.200702151
language
English
LU publication?
no
id
ec800267-b6fc-4de1-ad6f-46240c24e536
date added to LUP
2016-12-06 10:18:19
date last changed
2017-10-01 05:27:07
@article{ec800267-b6fc-4de1-ad6f-46240c24e536,
  abstract     = {<p>To search for functional links between glycosylphosphatidylinositol (GPI) protein monomer-oligomer exchange and membrane dynamics and confinement, we studied urokinase plasminogen activator (uPA) receptor (uPAR), a GPI receptor involved in the regulation of cell adhesion, migration, and proliferation. Using a functionally active fluorescent protein-uPAR in live cells, we analyzed the effect that extracellular matrix proteins and uPAR ligands have on uPAR dynamics and dimerization at the cell membrane. Vitronectin directs the recruitment of dimers and slows down the diffusion of the receptors at the basal membrane. The commitment to uPA-plasminogen activator inhibitor type 1-mediated endocytosis and recycling modifies uPAR diffusion and induces an exchange between uPAR monomers and dimers. This exchange is fully reversible. The data demonstrate that cell surface protein assemblies are important in regulating the dynamics and localization of uPAR at the cell membrane and the exchange of monomers and dimers. These results also provide a strong rationale for dynamic studies of GPI-anchored molecules in live cells at steady state and in the absence of cross-linker/clustering agents.</p>},
  author       = {Caiolfa, Valeria R and Zamai, Moreno and Malengo, Gabriele and Andolfo, Annapaola and Madsen, Chris D and Sutin, Jason and Digman, Michelle A and Gratton, Enrico and Blasi, Francesco and Sidenius, Nicolai},
  issn         = {0021-9525},
  keyword      = {Cell Line,Cell Membrane,Diffusion,Dimerization,Endocytosis,Extracellular Matrix,Fluorescence Resonance Energy Transfer,Glycosylphosphatidylinositols,Humans,Models, Biological,Plasminogen Activator Inhibitor 1,Protein Binding,Protein Transport,Receptors, Cell Surface,Receptors, Urokinase Plasminogen Activator,Serum,Vitronectin,Journal Article,Research Support, N.I.H., Extramural,Research Support, Non-U.S. Gov't},
  language     = {eng},
  month        = {12},
  number       = {5},
  pages        = {82--1067},
  publisher    = {Rockefeller University Press},
  series       = {Journal of Cell Biology},
  title        = {Monomer dimer dynamics and distribution of GPI-anchored uPAR are determined by cell surface protein assemblies},
  url          = {http://dx.doi.org/10.1083/jcb.200702151},
  volume       = {179},
  year         = {2007},
}